Bone is a living organ that is continuously being reshaped in a process called remodeling. In this process, cells called osteoclasts resorb bone tissues whereas cells called osteoblasts deposit new bone tissue. Osteoblasts can become trapped within the bone matrix they secrete, promoting their differentiation into osteocytes. These cells are thought to play an important role in sensing bone load. Under high loading conditions, osteoblasts increase bone mass, whereas under low loading conditions, osteoclasts remove bone tissue, optimizing its structure. Therefore, osteoclasts are closely related to bone loss or decreased bone density.
People may have bone loss or decreased bone density due to physiological factors or other external factors, which leads to osteoporosis. The signs of osteoporosis may include fracture, back pain, limited ability to act (even unable to move). Currently the treatment methods for osteoporosis include nutrition improvement, exercise, medication, etc. Regarding medication, drugs for clinical use comprise: estrogen or estrogen analogues, drugs for treatment of osteoporosis induced by glucocorticoid hormones, diphosphate, or calcitonin, etc. However, all these drugs described above have side effects, for example, diphosphate may cause nausea, indigestion, diarrhea, or constipation, and calcitonin may cause facial flushing, frequent urination, nausea, or itchy skin. Most of all, the drugs described above are unable to suppress the generation of osteoclasts cells, thus are unable to effectively cure osteoporosis.
Receptor activator of nuclear factor-κB ligand (RANKL) is a critical factor to induce the differentiation of osteoclasts from bone marrow-derived macrophages (BMM).